Wataru W. Sutow

Adult Wilms Tumor: Effect of Combined Therapy on Survival

Thirty-one adults with Wilms tumor were reported to the National Wilms Tumor Study from 1968 to 1979. Treatment and survival data for these patients were analyzed and compared to similar information derived from children enrolled in the first National Wilms Tumor Study. The ages of the 31 adults ranged from 17 to 63 years (mean 29 years). All but 3 patients had surgical resection or excision of tumor, 7 did not receive postoperative irradiation and all but 1 had chemotherapy. Actinomycin D and vincristine were the drugs used most commonly, 26 of the 31 patients receiving both agents. Advanced disease at diagnosis (6 stage III and 9 stage IV versus 9 stage I and 5 stage II--in 2 cases stage was not known) was found more often than in children in whom stages III and IV disease made up 27 per cent of the first National Wilms Tumor Study population. The 3-year actuarial survival rate for the 31 adults was 24 per cent: 48 per cent for stages I and II disease and 11 per cent for Stage IV disease. Comparable data for children in the first National Wilms Tumor Study, adjusted for stage, were 74, 87 and 53 per cent, respectively. It is concluded that adults with Wilms tumor treated as were these have a worse prognosis than children managed according to the first National Wilms Tumor Study regimen. However, those adults in this series who were treated aggressively, that is surgical excision, postoperative irradiation and multi-agent chemotherapy, appeared to have fared better than adults treated in the pre-chemotherapy era. It is concluded that aggressive therapy should be given to all adults with Wilms tumor irrespective of stage.

DECREASED RISK OF RADIATION-ASSOCIATED SECOND MALIGNANT NEOPLASMS IN ACTINOMYCIN-D-TREATED PATIENTS

One hundred two long‐term survivors of childhood cancers with second malignant neoplasms (SMNs) were collected from 10 institutions. Forty‐seven cases fulfilling study criteria were studied to determine the risk of developing a SMN in irradiated fields after exposure to various chemotherapeutic agents. The case control method was used. The risk of developing such tumors was decreased by a factor of 7 in patients receiving actinomycin‐D (AMD). The “protective” effect of AMD was more pronounced in patients receiving repeated courses of the agent. No change in relative risk was found for children given antifolates, the vinca alkaloids, or alkylating agents. AMD “protection” is an unexpected finding because the agent is an oncogen in animals and an enhancer of radiation, the latter being a known carcinogen. Possible mechanisms, which remain speculative, are discussed. These results indicate the need for careful long‐term observation of cancer survivors to gain understanding of the late effects of multimodal treatments.

Adjuvant chemotherapy in primary treatment of osteogenic sarcoma.A southwest oncology group study

A four‐drug adjuvant chemotherapy regimen (CONPADRI‐I) was utilized in the primary treatment of 18 children with osteogenic sarcoma. All patients had surgical amputation for the primary lesion. The children then received cyclophosphamide, vincristine, melphalan, and adriamycin in defined combinations intermittently over a 72‐week period. Of the 18 patients, 10 (55%) remain free of disease 24 months or longer from time of amputation.

Extrarenal Wilms tumor

The previous reports of extrarenal Wilms tumor are reviewed and two additional patients presented. The clinical and pathologic features are discussed. The diagnosis of extrarenal Wilms tumor does not imply a bad prognosis. Treatment should utilize multidrug chemotherapy similar to the guidelines set by the National Wilms Tumor Study.

Vincristine in acute leukemia of childhood.

Ninety‐four children with acute leukemia refractory to other forms of chematherapy were treated by three dosage regimens of vincristine. Complete remission occurred in 21.8% of the children experiencing adequate drug trial, with partial remission in 25.4% and bone marrow remission in 37.4%. Rapidity of response was variable with bone marrow remission occurring between the fourteenth and eighty‐fifth day of therapy and optimum response between the twenty‐first and one hundred and thirteenth day. Remissions, lasting only 20‐154 days, on maintenance therapy with vincristine tended to be relatively short‐lived, compared with those maintained by other agents. Toxicity of vincristine proved to be a limiting lactor, requiring alteration of therap in over 25% of the children treated. Vincristine, nevertheless, is firmly established as a valuable agent for the induction of remission in acute leukemia. Continuing studies indicate that the rate of remission reinduction is markedly increased by the combination of vincristine with prednisone.

Long‐term results of reinforcement therapy in children with acute leukemia

A total of 180 children with acute leukemia was randomized to one of two induction regimens: vincristine plus prednisone, or 6‐mercaptopurine plus prednisone. Of 170 patients evaluable for induction therapy, a hematologic remission was achieved in 83% (72/87) on vincristine plus prednisone, and in 93% (77/83) on 6‐mercaptopurine plus prednisone. When hematologic remission was achieved, patients were randomized to one of three maintenance schedules: 6‐mercaptopurine alone, 6‐mercaptopurine plus prednisone for 4 weeks every 3 months, or 6‐mercaptopurine plus prednisone plus vincristine for 4 weeks every 3 months. The durations of hematologic remission were compared from the achievement of hematologic remission to bone marrow relapse. The survival data were presented as an overview of the effect of this initial therapy on duration of survival. There was no statistical difference between the two induction regimens. The most important finding in the comparison of the three maintenance schedules was that reinforcement of 6‐mercaptopurine maintenance therapy with either prednisone or prednisone plus vincristine resulted in significantly longer durations of remission. Vincristine added to prednisone for reinforcement after induction of remission by vincristine plus prednisone did not increase the duration of hematologic remission or survival over prednisone reinforcement alone.

Radiation Therapy in Management of Wilms's Tumor

The authors analyzed treatment results in 71 cases of Wilmss tumor. The abdominal control rate was higher in 42 patients receiving postoperative radiotherapy (85.5%) than in 6 patients not receiving such therapy (1/6). In patients treated by nephrectomy and postoperative radiation, the addition of chemotherapy improved survival (78.2 VS. 30%). Pulmonary metastasis did not necessarily denote a hopeless situation since a significant number of patients could be salvaged by concurrent radiotherapy and chemotherapy; higher control rates were achieved with total than with less-than-total thoracic irradiation. Relatively low-dose irradiation appeared sufficient in both abdominal and thoracic radiotherapy if chemotherapy was given concurrently.

The National Wilms’ Tumor Study: A Progress Report

Wilms’ tumor was virtually incurable before pediatric surgeons, notably Ladd1, perfected their surgical techniques. Steady improvements thereafter added radiation therapy2 and chemotherapy. The routine postoperative use of actinomycin-D, as reported by Farber3, produced a two-year survival rate of 81% in patients managed from the outset by an experienced team using combination therapy. Wolff and his colleagues4 demonstrated the value of cyclic actinomycin-D given over a prolonged period after operation, and otherss 5,6 showed that vincristine sulfate was effective in the management of these children.

Adriamycin in the treatment of childhood acute leukemia. A Southwest Oncology Group study.

Sixty‐six children with acute leukemia, in advanced stages of their disease and resistant to conventional chemotherapy, received adriamycin for remission induction. Seventeen of 46 (37%) evaluable children with acute lymphocytic leukemia achieved a complete remission, and 5 (11%) achieved a partial remission. Two of 12 evaluable children with acute myelogenous leukemia achieved a complete remission, while an additional 3 achieved a partial remission. Two children with erythroleukemia also achieved a complete remission. Previous therapy with daunorubicin did not affect the response rate. The main toxicities observed with adriamycin were myelosuppression, fever, nausea and vomiting, stomatitis, alopecia, and cardiac toxicity (ST segment changes and arrhythmias).

Successful treatment of inoperable embryonal rhabdomyosarcoma

Embryonal rhabdomyosarcoma, when inoperable or metastatic, has usually ben a rapidly fatal cancer. Intensive combination chemotherapy (VAC) with Vincristine (VCR), Actinomycin-D (AMD) and Cyclophosphamide (CYT) in conjunction with radiotherapy is effective in the treatement of this tumor. Twenty-one children with inoperable or metastatic embryonal rhabdomyosarcoma, or undifferentiated sarcoma suggestive of embryonal rhabdomyosarcoma, were treated in the 3-year period 1967–1969. Sixteen of them (76%) are alive without evidence of disease 1–4 years after initiation of therapy. Therapy consisted of biopsy, Co80 radiation 5000–6000 rads tumor dose, and VAC chemotherapy. Surgery was subsequent;ly utilized when feasible. The chemotherapy consisted of VCR 2 mg./M2 IV weekly x12, AMD 75 MG./kG. divided into 5–8 daily doses every 3 months for 5 or 6 courses, and CYT given either as 2.5 mg./Kg./day for 2 years or 10 mg./Kg./day for 7 days every 6 weeks. The type of CYT therapy was dependent on tumour location and extent.